Journal of Medical Sciences1682-44741812-5727Asian Network for Scientific Information10.3923/jms.2007.516.525Abou-ShaabanRafiq R.A. Abou-AudaHisham S. 4200774The antioxidant and prolife rative activity of currently used antithyroid drugs
are known to cause agranulocytosis. In our previous work, the E-State approach
was used to introduce two new antithyroid drugs Abouthiouzine (ABZ) [1-n-butyl-3(isonicotinamido)-2-thiourea]
and Abouthiouline (ABL) [1-cyclohexyl-3(3-quinolyl)-2-thiourea] with modified
acyclic thiourylene structure to reduce antioxidative and mutagenic activity.
This study was conducted to compare the antioxidant, phagocytic, clastogenic
and proliferative effects of our newly designed antithyroid agents with propylthiouracil,
methimazole and thyroxine. Different experiments were undertaken on the agents
to investigate their antioxidant and proliferative activities. Chemiluminescences
(CL) response and phagocytic activity on isolated polymorphonuclear leukocytes
(PMNLs) were used to evaluate antioxidant effects. Micronucleus test on femoral
cells of mice as well as protein and nucleic acids level in hepatic cells were
also used to investigate proliferative and mutagenic effects. It was found that
all compounds except abouthiouzine inhibited the CL response and suppressed
the phagocytic activity; however, the intensity was comparatively less than
that of propylthiouracil. Cytological studies demonstrated that none of the
compounds were clastogenic, however, the ratio of polychromatic erythrocytes
(PCE) to normochromatic erythrocytes (NCE) was found to be increasing by the
treatment with propylthiouracil, methimazole and thyroxine, whereas this ratio
was comparatively less after treatment with Compounds I and IV, Abouthiouline
and Abouthiouzine. These results were supported by biochemical analysis. The
newly synthesized antithyroid drugs reduced the antioxidative and proliferative
activity as compared to propylthiouracil and methimazole. Further studies are
warranted to determine the exact mode of action of these compounds before clinical
trials are undertaken to suppress agranulocytosis.]]>Abou-Shaaban, R.R.A.,19953122Abou-Shaaban, R.R.A., H.A. Al-Khamees, H.S. Abou-Auda and A.P. Simonelli,19953180195Abou-Shaaban, R.R.A.,199641022Abou-Shaaban, R.R.A., H.A. Al-Khamees, H.S. Abou-Auda and A.P. Simonelli,199613129136Abou-Auda, H.S. and R.R. Abou-Shaaban,2006143441Allen, R.C. and L.D. Loose,197669245252Bartalena, L., F. Bogazzi and E. Martino,1996155363Bregman, A.A.,1983pp: 51-60pp: 51-60Cooper, D.S.,198431113531362Fidelus, R.K. and M.F. Tsan,198697155163Fidelus, R.K., P. Ginouves, D. Lawrence and M.F. Tan,1987170269275Giuriato, L., A.C. Borrione, A.M. Zanellato, M. Tonello and M. Scatena et al.,19911113761389Hicks, M., L.S. Wong and R.O. Day,199243439444Karlsson, F.A. and T.H. Totterman,198874258263Kier, L.B. and L.H. Hall,19907801807Lamm, D.C.C. and R.H. Lindsay,19792822892296Lowry, O.H., N.J. Rosebrough, A.L. Farr and R.J. Randall,1951193265275Matsunaga, M., K. Eguchi, T. Fukuda, H. Tezuka and Y. Ueki et al.,1988119413419Matty, M.J., M.A. Chaudhry and K.P. Lone,198247497507Medda, A.K. and A.K. Ray,1979Ophicephalus punctatus).]]>377480Pearce, S.H.S.,200461589594Redmond, O. and A.R. Tuffery,19811333747Schmid, W.,197531915Sterling, K., G. Tsuboyama and M.A. Brenner,198814109116Suthanthiran, M., M.E. Anderson, V.K. Sharma and A. Meister,19908733433347Tawfik, A.F., H.A. Shoeb, S.J. Bishop, F.L. Al?Shammary and A.M. Shibl,19902300305Van Haaster, H., F.H. De Jong, R. Docter and D.G. De Rooij,199213115741576Wall, J.R., S.L. Fang, T. Kurocki, S.H. Lagbar and L.E. Braverman,1984In vitro immunoactivity to propylthiouracil, methimazole and carbimazole in patients with Graves' disease: A possible cause of antithyroid drug-induced agranulocytosis.]]>58868872Wilson, R., J.H. McKillop, M. Travers, J. Smith, E. Smith and J.A. Thomson,1990122605609Wu, J., E.M. Levy and P.H. Black,198977710